Fungicidal aniline derivatives

ABSTRACT

A compound of the formula: ##STR1## useful as a fungicidal agent against phytopathogenic fungi, and particularly against strains resistant to benzimidazole, thiophanate and/or cyclic imide fungicides.

This is a continuation-in-part application of our copending application Ser. No. 485,295 filed on Apr. 15, 1983.

This invention relates to fungicidal aniline derivatives.

Benzimidazole and thiophanate fungicides such as Benomyl (methyl 1-(butylcarbamoyl)benzimidazol-2-ylcarbamate), Fubelidazol (2-(2-furyl)benzimidazole), Thiabendazole (2-(4-thiazolyl)benzimidazole), Carbendazim (methyl benzimidazol-2-ylcarbamate), Thiophanate-methyl (1,2-bis(3-methoxycarbonyl-2-thioureido)benzene), Thiophanate (1,2-bis(3-ethoxycarbonyl-2-thioureido)benzene), 2-(O,S-dimethylphosphorylamino)-1-(3'-methoxycarbonyl-2'-thioureido)benzene and 2-(O,O-dimethylthiophosphorylamino)-1-(3'-methoxycarbonyl-2'-thioureido)benzene are known to show an excellent fungicidal activity against various plant pathogenic fungi, and they have been widely used as agricultural fungicides since 1970. However, their continuous application over a long period of time provides phytopathogenic fungi with tolerance to them, whereby their plant disease-preventive effect is much lowered. Further, the fungi which gained tolerance to certain kinds of benzimidazole or thiophanate fungicides also show considerable tolerance to some other kinds of benzimidazole or thiophanate fungicides. Thus, they are apt to obtain cross-tolerance. Therefore, if any material decrease of their plant disease-preventive effect in certain fields is observed, their application to such fields has to be discontinued. But, it is often observed that the density of drug-resistant organisms is not decreased even long after the discontinuation of the application. Although other kinds of fungicides have to be employed in such case, only few are so effective as benzimidazole or thiophanate fungicides in controlling various phytopathogenic fungi. Cyclic imide fungicides such as Procymidone (3-(3', 5'-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximide), Iprodione (3-(3', 5'-dichlorophenyl)-1-isopropylcarbamoylimidazolidine-2,4-dione), Vinchlozolin (3-(3', 5'-(dichlorophenyl)-5-methyl-5-vinyloxazolidine-2,4-dione), ethyl (RS)-3-(3', 5'-dichlorophenyl)-5-methyl-2,4-dioxooxazolidine-5-carboxylate, etc., which are effective against various plant diseases, particularly those caused by Botrytis cinerea, have the same defects as previously explained with respect to the benzimidazole and thiophanate fungicides.

In C.R. Acad. Sc. Paris, t. 289, S'erie D, pages 691-693 (1979), it is described that such herbicides as Barban (4-chloro-2-butynyl N-(3-chlorophenyl)carbamate), Chlorobufam (1-methyl-2-propynyl N-(3-chlorophenyl)carbamate), Chlorpropham (isopropyl N-(3-chlorophenyl)carbamate) and Propham (isopropyl N-phenylcarbamate) exhibit a fungicidal activity against certain organisms tolerant to some of the benzimidazole or thiophanate fungicides. However, their fungicidal activity against the drug-resistant fungi is not strong enough, and hence, practically they can not be used as fungicides.

As a result of a study seeking a new type of fungicides, it has now been found that aniline derivatives of the formula: ##STR2## wherein X and Y are, the same or different, each a hydrogen

a halogen atom, a lower alkyl group, a halo(lower)-alkyl group, a lower alkenyl group, a lower alkynyl group, a cyano group, a hydroxyiminomethyl group, a lower alkoxy-iminomethyl group or a group of the formula: --CH₂ OR₂, ##STR3## in which R₂ is a lower alkyl group, R₃ is a lower alkyl group, a lower alkenyl group or a lower alkynyl group and R₄ is a lower alkylene group, with the proviso that when either one of X and Y is a hydrogen atom, the other is not a hydrogen atom; R₁ is a halo(lower)alkenyl group, a halo(lower)alkynyl group, a cyano group, a hydroxy(lower)alkyl group, a lower alkoxy(lower)alkenyl group, a lower alkoxy(lower)alkynyl group, a cyano(lower)alkyl group or a group of the formula: --CH₂ R₅, ##STR4## or --SO₂ R₇ in which R₅ is a lower alkoxy-carbonyl group, an acyl group (e.g. lower alkanoyl, benzoyl) or a lower alkylthio group, R₆ is a lower alkyl group, a lower alkoxy group or a lower alkylamino group and R₇ is a lower alkyl group, a halo(lower)alkyl group or a lower alkylamino group; Z is a hydrogen atom, a hydroxyl group, a lower alkoxy group, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower alkoxycarbonyl-(lower) alkyl group, a lower alkoxycarbonyloxy group, a lower alkylcarbonyloxy group or a group of the formula: ##STR5## or --SR₉ in which R₈ is a lower alkyl group, a cyclo(lower)-alkyl group, a halo(lower)alkyl group, a lower alkoxyalkyl group or a phenyl group and R₉ is a lower alkyl group, a lower alkoxycarbonyl group or a phenyl group; A is an oxygen atom or a sulfur atom; and B is a lower alkyl group, a lower alkenyl group, a cyclo(lower)alkyl group, a phenyl group or a group of the formula: -W-R₁₀ in which W is an oxygen atom or a sulfur atom and R₁₀ is a cyclo(lower)alkyl group, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a halo(lower)alkenyl group, a halo(lower)alkynyl group, a phenyl group, a phenyl group substituted with a halogen atom, a cyclo(lower)alkyl(lower)alkyl group or a lower alkyl group substituted with a member selected from the group consisting of halogen, cyano, lower alkoxy, phenyl, lower alkenyloxy, halo(lower)alkoxy, phenoxy and ar(lower)alkoxy (e.g. phenyl(lower)alkoxy), show an excellent fungicidal activity against plant pathogenic fungi which have developed resistance to benzimidazole, thiophanate and/or cyclic imide fungicides. It is notable that their fungicidal potency against the organisms tolerant to benzimidazole, thiophanate and/or cyclic imide fungicides (hereinafter referred to as "drug-resistant fungi" or "drug-resistant strains") is much higher than that against the organisms sensitive to benzimidazole, thiophanate and/or cyclic imide fungicides (hereinafter referred to as "drug-sensitive fungi" or "drug-sensitive strains").

The term "lower" used hereinabove and hereinafter in connection with alkyl, alkenyl, alkynyl, alkylene, alkoxy, etc. is intended to have not more than 6 carbon atoms.

Among the compounds of the formula (I), 3,5-dichloro-4-cyanooxymethacrylanilide and 3-methyl-4-cyanooxymethacrylanilide (Belgian Pat. No. 670,675) and 2-chloro-4-acetylamino-6-methylphenyl N-methylcarbamate (Nippon Oyo Dobutsu Konchu Gakkai-Shi (Journal of Japanese Applied Animal and Insecticidal Research Organization), 12 (4), 202-210 (1968)) are known. However, it has not been known or reported that they have any fungicidal activity or are useful as fungicides.

The compounds (I) are fungicidally effective against a wide scope of plant pathogenic fungi, of which examples are as follows: Podosphaera leucotricha, Venturia inaequalis, Mycosphaerella pomi, Marssonina mali and Sclerotinia mali of apple, Phyllactinia kakicola and Gloeosporium kaki of persimmon, Cladosporium carpophilum and Phomopsis sp. of peach, Cercospora viticola, Uncinula necator, Elsinoe ampelina and Glomerella cingulata of grape, Cercospora beticola of sugarbeet, Cercospora arachidicola and Cercospora personata of peanut, Erysiphe graminis f. sp. hordei, Cercosporella herpotrichoides and Fusarium nivale of barley, Erysiphe graminis f. sp. tritici of wheat, Sphaerotheca fuliginea and Cladosporium cucumerinum of cucumber, Cladosporium fulvum of tomato, Corynespora melongenae of eggplant, Sphaerotheca humuli, Fusarium oxysporum f. sp. fragariae of strawberry, Botrytis alli of onion, Cercospora apii of celery, Phaeoisariopsis griseola of kidney bean, Erysiphe cichoracearum of tobacco, Diplocarpon rosae of rose, Elsinoe fawcetti, Penicillium italicum, Penicillium digitatum of orange, Botrytis cinerea of cucumber, eggplant, tomato, strawberry, pimiento, onion, lettuce, grape, orange, cyclamen, rose or hop, Sclerotinia sclerotiorum of cucumber, eggplant, pimiento, lettuce, celery, kidney bean, soybean, azuki bean, potato or sunflower, Sclerotinia cinerea of peach or cherry, Mycosphaerella melonis of cucumber or melon, etc. Namely, the compounds (I) are highly effective in controlling the drug-resistant strains of said fungi.

The compounds (I) are also fungicidally effective against fungi sensitive to said known fungicides as well as fungi to which said known fungicides are ineffective. Examples of such fungi are Pyricularia oryzae, Pseudoperonospora cubensis, Plasmopara, viticola, Phytophthora infestans, etc.

Advantageously, the compounds (I) are of low toxicity and have little detrimental actions on mammals, fishes and so on. Also, they may be applied to the agricultural field without causing any material toxicity to important crop plants.

In view of their excellent fungicidal properties, particularly useful is a compound of the formula: ##STR6## wherein X, Y and B are each as defined above, or a compound of the formula: ##STR7## wherein X and Y are, the same or different, each a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a group of the formula: --CH₂ OR₂ or ##STR8## in which R₂ is a lower alkyl group, X and Y being simultaneously not hydrogen; R₁ is a cyano group, a cyano(lower)alkyl group or a group of the formula: --CH₂ R₅, ##STR9## or --SO₂ R₇ in which R₅ is a lower alkylthio group, R₆ is a lower alkyl group, a lower alkoxy group or a lower alkylamino group and R₇ is a lower alkyl group, a halo(lower)alkyl group or a lower alkylamino group; A is an oxygen atom or a sulfur atom and B is a group of the formula: -W-R₁₀ in which W is an oxygen atom or a sulfur atom and R₁₀ is a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a halo(lower)-alkyl group or a lower alkoxy(lower)alkyl group.

Thus, the present invention provides a fungicidal aniline derivative of the formula (I). It also provides a fungicidal composition which comprises, as an active ingredient, a fungicidally effective amount of the compound (I) and an inert carrier or diluent. It also provides a combination composition comprising as active ingredients the compound (I) together with at least one of benzimidazole, thiophanate and/or cyclic imide fungicides, which is fungicidally effective against not only drug-sensitive fungi but also drug-resistant fungi, and hence particularly effective for the prevention of plant diseases. It further provides a method of controlling plant pathogenic fungi including drug-resistant strains and drug-sensitive strains applying a fungicidally effective amount of the compound (I) to plant pathogenic fungi. It furthermore provides a process for producing the compound (I).

The compound of the formula (I) may be prepared by any one of the following procedures:

Procedure (a):

The compound (I) is prepared by reacting a compound of the formula: ##STR10## wherein X, Y, R₁ and Z are each as defined above, with a halide of the formula: ##STR11## wherein A and B are each as defined above and R₁₁ is a halogen atom, or with an anhydride of the formula: ##STR12## wherein A is as defined above and B' is a lower alkyl group, a lower alkenyl group, a lower cycloalkyl group or a phenyl group.

The reaction is usually carried out in the presence of an inert solvent (e.g. benzene, toluene, tetrahydrofuran, chloroform, ethyl acetate, dimethylformamide). If desired, the reaction may be performed in the existence of a base (e.g. triethylamine, sodium hydroxide, N,N-diethylaniline) so as to obtain the compound (I) in a high yield. The reaction may be accomplished at a temperature of 0° to 150° C. instantaneously or within 12 hours.

Procedure (b):

The compound of the formula (I) wherein Z is a hydrogen atom and B is a group of the formula: -W-R₁₀ in which W and R₁₀ are each as defined above is also prepared by reacting a compound of the formula: ##STR13## wherein X, Y, R₁ and A are each as defined above, with an alcohol or thioalcohol of the formula:

    H-W-R.sub.10

wherein W and R₁₀ are each as defined above.

The reaction is usually carried out in the presence of an inert solvent (e.g. benzene, toluene, xylene, diethyl ether, tetrahydrofuran, dioxane, dimethylformamide, chloroform, carbon tetrachloride). If desired, the reaction may be performed in the existence of a catalyst (e.g. triethylamine, N,N-diethylaniline, 1,4-diazabicyclo[2.2.2]-octane) so as to obtain the compound (I) in a high yield. The reaction may be accomplished at a temperature of 0° to 50° C. instantaneously or within 10 hours.

The starting compound (III) can be prepared by reacting a compound of the formula: ##STR14## wherein X, Y and R₁ are each as defined above with phosgene or thiophosgene.

The reaction is usually carried out in the presence of an inert solvent (e.g. benzene, toluene, xylene, ethyl acetate). The reaction may be accomplished at a temperature of 50° C. to the boiling point of the solvent instantaneously or within 10 hours.

The compound (IV) can be prepared by reduction of a nitrobenzene of the formula: ##STR15## wherein X, Y and R₁ are each as defined above according to a conventional reduction procedure. A typical example of such reduction procedure is illustratively shown below.

3-Propionyl-4-cyanomethoxy-5-methylnitrobenzene (X ═CH₃ ; ##STR16## R₁ ═-CH₂ C.tbd.N) (4.96 g) in acetic acid (60 ml) was dropwise added to an aqueous solution (300 ml) containing acetic acid (15 ml) and iron (20 g). The resulting mixture was kept at 40° C. for 4 hours with vigorous stirring. The solid was removed by filtration, and the filtrate was extracted with dichloromethane. The extract was washed with an aqueous solution of potassium carbonate and water, dried over magnesium sulfate and concentrated under reduced pressure to give 3-propionyl-4-cyanomethoxy-5-methylaniline (3.88 g) in a yield of 88.8%. NMR δ (CDCl₃): 1.18 (t, 3H), 2.30 (s, H), 2.85 (q, 2H), 4.61 (s, 2H), 6.68 (s, 2H).

Procedure (c):

The compound (I) is also prepared by reacting a compound of the formula: ##STR17## wherein X, Y, R₁, A and B are each as defined above, with a compound of the formula:

    Z-R.sub.12

wherein Z is as defined above and R₁₂ is a leaving group (e.g. tosyloxy, mesyloxy, halogen).

The reaction is usually carried out in the presence of an inert solvent (e.g. benzene, toluene, xylene, dioxane, chloroform). If desired, a base (e.g. triethylamine, sodium hydroxide, sodium hydride) may be present in the reaction system. The reaction may be accomplished at a temperature of 0° to 150° C. instantaneously or within 12 hours.

Procedure (d):

The compound (I) is also prepared by reacting a phenol of the formula: ##STR18## wherein X, Y, Z, A and B are each as defined above, with a compound of the formula:

    R.sub.1 -R.sub.13

wherein R₁ is as defined above and R₁₃ is a leaving group (e.g. tosyloxy, mesyloxy, halogen).

The reaction is usually carried out in the absence or presence of an inert solvent (e.g. water, benzene, toluene, tetrahydrofuran, dimethylsulfoxide, dimethylformamide using a dehydrohalogenating agent (e.g. sodium hydroxide, potassium carbonate, sodium hydride) at a temperature of 10° to 100° C. for a period of 30 minutes to 12 hours.

The phenol of the formula (VII) wherein Z is a hydrogen atom can be prepared by reacting a 4-aminophenol of the formula: ##STR19## wherein X and Y are each as defined above, with a chloride of the formula: ##STR20## wherein A and B are each as defined above.

The reaction between the 4-aminophenol (VIII) and the chloride is usually carried out in an inert solvent (e.g. benzene, toluene, xylene, diethyl ether, tetrahydrofuran, dioxane, chloroform, carbon tetrachloride, ethyl acetate, pyridine, dimethylformamide) in the presence of a dehydrohalogenating agent (e.g. pyridine, triethylamine, N,N-diethylaniline, sodium hydroxide, potassium hydroxide) at a temperature of 0 to 150° C. instantaneously or within 10 hours.

The phenol of the formula (VII) wherein Z is a hydrogen atom and B is a group of the formula: -W-R₁₀ in which W and R₁₀ are each as defined above, can be also prepared by reacting a 4-hydroxyphenyl isocyanate of the formula: ##STR21## wherein X, Y and A are each as defined above, with an alcohol or thioalcohol of the formula:

    H-W-R.sub.10

wherein W and R₁₀ are each as defined above.

The reaction between the 4-hydroxyphenyl isocyanate (IX) and the alcohol or thioalcohol can be carried out in the absence or presence of an inert solvent (e.g. toluene, xylene, diethyl ether, tetrahydrofuran, dioxane, dimethylformamide, chloroform, carbon tetrachloride). If desired, the reaction may be performed in the presence of a catalyst (e.g. triethylamine, N,N-diethylaniline 1,4-diazabicyclo[2.2.2]octane). The reaction is performed at a temperature of 0° to 50° C. instantaneously or within 10 hours.

Still, the 4-hydroxyphenyl isocyanate (IX) can be prepared by reacting the 4-aminophenol (VIII) with phosgene or thiophosgene.

The reaction between the 4-aminophenol (VIII) and phosgene or thiophosgene can be carried out in an inert solvent (e.g. benzene, toluene, ethyl acetate) at a temperature of 50° C. to the boiling point of the solvent within 30 minutes to 10 hours.

The aminophenol (VIII) can be prepared by reducing a 4-nitrophenol of the formula: ##STR22## wherein X and Y are each as defined above according to a conventional reduction procedure. In case of catalytic hydrogenation, for example, the reaction may be carried out in an inert solvent (e.g. ethyl acetate, ethanol) in the presence of a catalyst (e.g. platinum oxide, palladium on carbon) at a temperature of 0° to 60° C. under hydrogen gas.

The 4-nitrophenol (X) can be prepared, for example, by the method described in the literature [J. Org. Chem., 27, 218 (1962)].

Procedure (e):

Further, the compound (I) wherein X is a hydroxyiminomethyl group or a lower alkoxyiminomethyl group can be prepared by reacting a benzaldehyde of the formula: ##STR23## wherein Y, Z, A, B and R₁ are each as defined above, with an equimolar or excess amount of hydroxylamine or a lower alkoxyamine in an inert solvent (e.g. methanol, ethanol). The reaction may be brought to completion in about 0.5 to 12 hours.

The above-mentioned procedures are summarized in the following reaction scheme: ##STR24##

Some typical examples for preparation of the compound (I) are illustratively shown below.

EXAMPLE 1

Preparation of isopropyl N-(3-chloro-4-methylcarbamoyloxy-5-methoxymethylphenyl)carbamate according to Procedure (a):

3-Chloro-4-methylcarbamoyloxy-5-methoxymethylaniline (1.0 g) and N,N-diethylaniline (0.90 g) were dissolved in toluene (15 ml). To the resultant solution was dropwise added isopropyl chloroformate (0.75 g) in 5 minutes under ice-cooling. The resultant mixture was allowed to stand at room temperature for 12 hours, poured into ice-water and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a mixture of benzene and tetrahydrofuran as the eluent to give isopropyl N-(3-chloro-4-methylcarbamoyloxy-5-methoxymethylphenyl)carbamate (Compound No. 4) (1.22 g) in a yield of 90.5%. M.P., 113°-114° C.

Elementary analysis: Calcd. for C₁₄ H₁₉ N₂ ClO₅ : C, 50.84%; H, 5.79%; N, 8.47%; Cl, 10.72%. Found: C, 50.81%; H, 5.88%; N, 8.35%; Cl, 10.92%.

EXAMPLE 2

Preparation of isopropyl N-[3-chloro-4-(3-cyanopropyloxy)-5-methoxymethylphenyl]carbamate according to Procedure (b):

3-Chloro-4-(3-cyanopropyloxy)-5-methoxymethylaniline (2.55 g) in toluene (20 ml) was dropwise added to a toluene solution containing 10 g of phosgene at 10° to 20° C. The resulting mixture was gradually heated and, after being refluxed for 30 minutes, cooled to room temperature. The solvent was removed by distillation under reduced pressure to give 3-chloro-4-(3-cyanopropyloxy)-5-methoxymethylphenyl isocyanate (2.80 g). The thus obtained crude substance was added to a toluene solution (50 ml) containing triethylamine (1.0 g) and isopropanol (1.0 g). The resultant mixture was allowed to stand at room temperature for 12 hours, poured into ice-water and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a mixture of toluene and ethyl acetate as the eluent to give isopropyl N-[3-chloro-4-(3-cyanopropyloxy)-5-methoxymethylphenyl]carbamate (Compound No. 6) (2.70 g) in a yield of 79.2%. n_(D) ²⁰.0 1.5196.

NMR δ (CDCl₃): 7.42 (d, 1H), 7.12 (d, 1H), 6.77 (broad, 1H), 4.92 (m, 1H), 4.45 (s, 2H), 3.95 (t, 2H), 3.37 (s, 3H), 2.65 (t, 2H), 2.18 (m, 2H), 1.25 (d, 6H).

EXAMPLE 3

Preparation of isopropyl N-methyl-N-(3-chloro-4-cyanomethoxy-5-methoxymethylphenyl)carbamate according to Procedure (c):

Isopropyl N-(3-chloro-4-cyanomethoxy-5-methoxymethylphenyl)carbamate (3.13 g) and iodomethane (4.30 g) were dissolved in tetrahydrofuran (10 ml). The resultant solution was dropwise added to a tetrahydrofuran solution (20 ml) containing potassium hydroxide (1.68 g) and tetra-n-butylammonium bromide (1.0 g). After being allowed to stand at room temperature for 12 hours, the reaction mixture was poured into ice-water and extracted with toluene. The extract was washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a mixture of toluene and ethyl acetate as the eluent to give isopropyl N-methyl-N-(3-chloro-4-cyanomethoxy-5-methoxymethylphenyl)carbamate (Compound No. 41) (3.06 g) in a yield of 93.5%. n_(D) ²².0 1.5123.

EXAMPLE 4

Preparation of isopropyl N-(3-chloro-4-cyanomethoxy-5-methoxymethylphenyl)carbamate according to Procedure (d):

3-Chloro-4-hydroxy-5-methoxymethylaniline (52.8 g) and N,N-diethylaniline (42.0 g) were dissolved in ethyl acetate (300 ml). To the resultant solution was dropwise added isopropyl chloroformate (34.6 g) in 15 minutes under ice-cooling. After being allowed to stand at room temperature for 12 hours, the reaction mixture was poured into ice-water. The organic layer was washed with dilute hydrochloric acid and water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using toluene and ethyl acetate as the eluent to give isopropyl N-(3-chloro-4-hydroxy-5-methoxymethylphenyl)carbamate (65.6 g). Sodium hydride (9.60 g, 60% dispersion in mineral oil) was added to dimethylformamide (240 ml). To the resultant mixture was added isopropyl N-(3-chloro-4-hydroxy-5-methoxymethylphenyl)carbamate (65.6 g) under 5° C. The resulting solution was stirred at a temperature of 20° C. for 30 minutes, and chloroacetonitrile (19.0 g) was added thereto in 5 minutes. The mixture was heated at 90° C. for 10 minutes, poured into ice-water and extracted with ethyl acetate. The extract was washed with aqueous potassium carbonate solution and water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using toluene and ethyl acetate as the eluent to give isopropyl N-(3-chloro-4-cyanomethoxy-5-methoxymethylphenyl)carbamate (Compound No. 5) (67.5 g) in a yield of 76.8%. M.P., 58.5°-60.5° C.

Elementary analysis: Calcd. for C₁₄ H₁₇ N₂ O₄ Cl: C, 53.77%; H, 5.48%; N, 8.96%; Cl, 11.34%. Found: C, 53.77%; H, 5.57%; N, 8.88%; Cl, 11.60%.

EXAMPLE 5

Preparation of isopropyl N-(3-methyl-4-methylthiomethyloxy-5-n-propylphenyl)carbamate according to Procedure (d):

A mixture of 3-methyl-4-hydroxy-5-n-propylaniline (1.65 g) and ethyl acetate (20 ml) was added to an ethyl acetate solution containing 10 g of phosgene at 0° to 5° C. The resulting mixture was gradually heated and, after the solution became clear, cooled to room temperature. The solvent was removed by distillation under reduced pressure to give 3-methyl-4-hydroxy-5-n-propylphenyl isocyanate. the thus obtained crude substance was added to a toluene solution (50 ml) containing triethylamine (1.0 g) and isopropanol (1.0 g). The resultant mixture was allowed to stand at room temperature for 12 hours, poured into ice-water and extracted with ethyl acetate. The extract was washed with dilute hydrochloric acid and water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a mixture of toluene and ethyl acetate as the eluent to give isopropyl N-(3-methyl-4-hydroxy-5-n-propylphenyl)carbamate (1.70 g). Sodium hydride (0.28 g, 60% dispersion in mineral oil) was added to dimethylformamide (50 ml). To the resulting mixture was added isopropyl N-(3-methyl-4-hydroxy-5-n-propylphenyl)carbamate (1.70 g) under 5° C. The resulting solution was stirred at a temperature of 20° C. for 30 minutes, and (chloromethyl)methylsulfide (0.67 g) was added thereto in 5 minutes. The mixture was heated at 90° C. for 10 minutes, poured into ice-water and extracted with ethyl acetate. The extract was washed with aqueous potassium carbonate solution and water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a mixture of toluene and ethyl acetate as the eluent to give isopropyl N-(3-methyl-4-methylthiomethyloxy-5-n-propylphenyl)carbamate (Compound No. 14) (1.90 g) in a yield of 61.0%. n_(D) ²¹.4

NMR δ (CDCl₃): 7.01 (s, 2H), 6.45 (broad, 1H), 4.99 (m, 1H), 4.86 (s, 2H), 2.65 (t, 2H), 2.35 (s, 3H), 2.34 (s, 3H), 1.29 (d, 6H), 0.80-1.50 (m, 5H).

EXAMPLE 6

Preparation of isopropyl N-(3-methoxy-4-cyanomethoxy-5-methoxyiminomethylphenyl)carbamate according to Procedure (e):

Isopropyl N-(3-methoxy-4-cyanomethoxy-5-formylphenyl)carbamate (0.59 g) was dissolved in ethanol (20 ml). To the solution was added an aqueous solution (10 ml) containing sodium hydroxide (0.32 g) and methoxyamine hydrochloride (0.66 g). After being allowed to stand for 12 hours, the reaction mixture was concentrated in vacuo, and the residue was dissolved in ethyl acetate. The resultant solution was washed with water, dried over magnesium sulfate and concentrated under reduced pressure to give isopropyl N-(3-methoxy-4-cyanomethoxy-5-methoxyiminomethylphenyl)carbamate (Compound No. 78) (0.62 g) in a yield of 94.5%.

According to any one of Procedures (a), (b), (c), (d) and (e), the aniline derivatives of the formula (I) as shown in Table 1 can be prepared:

    TABLE 1       ##STR25##       Compound        No. X Y R.sub.1 Z A B Physical Constant               1 H OC.sub.2       H.sub.5      ##STR26##       H O O(i)Pr M.P. 93--94° C.  2 Cl CH.sub.2       OCH.sub.3      ##STR27##       H O O(i)Pr n.sub.D.sup.26.1 1.5142  3 Cl CH.sub.2       OCH.sub.3      ##STR28##       H O O(i)Pr M.P. 90-92° C.  4 Cl CH.sub.2       OCH.sub.3      ##STR29##       H O O(i)Pr M.P. 113-114° C.   5 Cl CH.sub.2 OCH.sub.3 CH.sub.2   N      C  H O O(i)Pr M.P. 58.5-60.5° C. 6 Cl CH.sub.2       OCH.sub.3 (CH.sub.2).sub.3 CN H O O(i)Pr n.sub.D.sup.20.0 1.5196 7 Cl      CH.sub.2 OCH.sub.3 CH.sub.2 SCH.sub.3 H O O(i)Pr n.sub.D.sup.20.0 1.5471      8 Cl CH.sub.2 OCH.sub.3 SO.sub.2 CH.sub.3 H O O(i)Pr n.sub.D.sup.22.0      1.5266 9 Cl CH.sub.2 OCH.sub.3 SO.sub.2 CF.sub.3 H O O(i)Pr M.P.      96-98° C. 10 Cl CH.sub.2 OCH.sub.3 SO.sub.2 NH(n)Pr H O O(i)Pr      n.sub.D.sup.22.0 1.5250 11 CH.sub.3 CH.sub.3 CH.sub.2 C N H O O(i)Pr      M.P. 114-116° C.       12 CH.sub.3      ##STR30##       CH.sub.2 C N H O O(i)Pr M.P. 76-78° C.  13 Cl OC.sub.2 H.sub.5      CH.sub.2 CN H O O(i)Pr M.P. 89-91° C. 14 CH.sub.3 CH.sub.2      CH.sub.2 CH.sub.3 CH.sub.2 SCH.sub.3 H O O(i)Pr n.sub.D.sup.21.4 1.5299      15 Cl CH.sub.2 OCH.sub.3 CH.sub.2       CN H O      ##STR31##       n.sub.D.sup.22.0 1.5383  16 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O       ##STR32##       n.sub.D.sup.19.7 1.5350  17 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O       ##STR33##       n.sub.D.sup.22.0 1.5191  18 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O      OCH.sub.2 CH.sub.2 F n.sub.D.sup.22.0 1.5280 19 Cl CH.sub.2 OCH.sub.3      CH.sub.2 CN H O SC.sub.2 H.sub.5 n.sub.D.sup.22.0 1.5752 20 CH.sub.3      CH.sub.2 CHCH.sub.2 CH.sub.2 CN H O O(i)Pr n.sub.D.sup.22.3 1.5275  21      CH.sub.3       ##STR34##       CH.sub.2 CN H O O(i)Pr  22 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H S O(i)Pr      n.sub.D.sup.20.5 1.5733 23 Cl CH.sub.2 OCH.sub.3 CH.sub.2 C N H S S(i)Pr      n.sub.D.sup.20.5 1.5838 24 Cl CH.sub.2       OCH.sub.3 CN H O O(i)Pr n.sub.D.sup.23.0 1.5268 25 Cl CH.sub.2       OCH.sub.3 CH.sub.2 CH.sub.2 CN H O O(i)Pr n.sub.D.sup.20.8 1.5530 26 Br B      r CH.sub.2 CN H O O(i)Pr M.P. 143-144° C. 27 Br CCH CH.sub.2 CN H      O O(i)Pr NMR δ.sub.TMS.sup.CDCl.sbsp.3 : 1.21(d, 6H),      3.30(s, 1H), 4.70(s, 2H),        5.00(m, 1H), 7.25-7.80(3H) 28 Br      CH.sub.2 OCH.sub.3 CH.sub.2 CN H O O(i)Pr       29 Cl      ##STR35##       CH.sub.2 CN H O O(i)Pr       30 Cl      ##STR36##       CH.sub.2 CN H O O(i)Pr       31 Cl      ##STR37##       CH.sub.2 CN H O O(i)Pr  32 Cl NCHCH.sub.3 CH.sub.2 CN H O O(i)Pr 33      OC.sub.2 H.sub.5 CCH CH.sub.2 CN H O O(i)Pr 34 OC.sub.2 H.sub.5 CN      CH.sub.2 CN H O O(i)Pr       35 CH.sub.3      ##STR38##       CH.sub.2 CN H O O(i)Pr n.sub.D.sup.22.5 1.5290       36 CH.sub.3      ##STR39##       CH.sub.2 CN H O O(i)Pr M.P. 85-87° C.  37 CH(OCH.sub.3).sub.2      OC.sub.2 H.sub.5 CH.sub.2 CN H O O(i)Pr 38 CH(OC.sub.2 H.sub.5).sub.2      OC.sub.2 H.sub.5 CH.sub.2 CN H O O(i)Pr 39 CH(OC.sub.2 H.sub.5).sub.2      OCH.sub.3 CH.sub.2 CN H O O(i)Pr NMR δ.sub.TMS.sup.CDCl.sbsp.3 :      1.25(t, 6H),        1.30(d, 6H), 3.65(d, 4H),        3.91(s, 3H),      4.80(s, 2H),        5.05(m, 1H), 5.78(s, 1H),        6.88(d, 1H),      7.58(d, 1H)       40 CH.sub.3      ##STR40##       CH.sub.2 CN H O O(i)Pr  41 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN CH.sub.3 O O      (i)Pr n.sub.D.sup.22.0 1.5123 42 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN      CH.sub.2 CHCH.sub.2 O O(i)Pr n.sub.D.sup.20.8 1.5193 43 Cl CH.sub.2      OCH.sub.3 CH.sub.2 CN CH.sub.2 CCH O O(i)Pr n.sub.D.sup.20.0 1.5170 44      Cl CH.sub.2 OCH.sub.3  CH.sub.2       CN      ##STR41##       O O(i)Pr NMR δ.sub.TMS.sup.CDCl.sbsp.3 : 1.20(d, 6H),2.60(s, 3H),      3.40(s, 3H),4.54(s, 2H), 4.84(s, 2H),5.00(m, 1H), 7.14(s, 2H)  45 Cl      CH.sub.2 OCH.sub.3 CH.sub.2       CN      ##STR42##       O O(i)Pr NMR δ.sub.TMS.sup.CDCl.sbsp.3 : 0.70-1.30 (m, 4H),      1.30(d, 6H), 2.80-3.10(m, 1H), 3.45(s, 3H),4.55(s, 2H), 4.81(s, 2H),4.98(      m, 1H), 7.12(s, 2H)  46 Cl CH.sub.2 OCH.sub.3 CH.sub.2       CN      ##STR43##       O O(i)Pr n.sub.D.sup.20.8 1.5513  47 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN       ##STR44##       O O(i)Pr  48 Cl CH.sub.2 OCH.sub.3 CH.sub.2       CN      ##STR45##       O O(i)Pr  49 Cl CH.sub.2 OCH.sub.3 CH.sub.2       CN      ##STR46##       O O(i)Pr  50 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN CH.sub.2 COOCH.sub.3 O      O(i)Pr n.sub.D.sup.23.2 1.5075 51 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN      SCH.sub.3 O O(i)Pr 52 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN SC.sub.6 H.sub.5      O O(i)Pr n.sub.D.sup.22.5 1.5583  53 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN       ##STR47##       O O(i)Pr n.sub.D.sup.23.2 1.5221  54 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN       ##STR48##       O O(i)Pr  55 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN OH O O(i)Pr  56 Cl      CH.sub.2 OCH.sub.3 CH.sub.2       CN H O      ##STR49##        n.sub.D.sup.24.0 1.5341  57 Cl CH.sub.2 OCH.sub.3 CH.sub.2       CN OCH.sub.3 O O(i)Pr  58 Cl CH.sub.2 OCH.sub.3 CH.sub.2       CN      ##STR50##       O O(i)Pr  59 Cl CH.sub.2 OCH.sub.3 CH.sub.2       C N      ##STR51##       O O(i)Pr       60 CH.sub.3      ##STR52##       CH.sub.2 CN H O O(i)Pr  61 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O       ##STR53##       n.sub.D.sup.24.0 1.5434  62 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O      CHCHCH.sub.3 n.sub.D.sup.24.0 1.5526 63 Cl CH.sub.2 OCH.sub.3 CH.sub.2      CN H O C.sub.6 H.sub.5 M.P. 101-102° C. 64 CH.sub.3 CH.sub.2      CNBrCH.sub.2 Br CH.sub.2       CN H O O(i)Pr NMR δ.sub.TMS.sup.CDCl.sbsp.3 : 1.30(d, 6H),      2.34(s, 3H), 4.63(s, 2H),        6.84(broad, 1H), 7.20(s, 2H)  65 Cl      CH.sub.2 OCH.sub.3 CH.sub.2       CN H O      ##STR54##       n.sub.D.sup.22.6 1.5400  66 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O       ##STR55##       n.sub.D.sup.23.8 1.5538  67 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O       ##STR56##        68 Cl CH.sub.2 OCH.sub.3 CH.sub.2       CN H O      ##STR57##       69 CH.sub.3      ##STR58##       CH.sub.2 CN H O O(i)Pr  70 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O      OCH.sub.2 CH.sub.2 CN M.P. 95-97° C.  71 Cl CH.sub.2 OCH.sub.3      CH.sub.2       CN H O      ##STR59##       n.sub.D.sup.28.9 1.5473       72 CH.sub.3      ##STR60##       CH.sub.2 CN H O O(i)Pr  73 CH.sub.3 CHNOCH.sub.3 CH.sub.2 CN H O O(i)Pr      74 CH.sub.3 OC.sub.2 H.sub.5 CH.sub.2 CN H O O(i)Pr 75 OCH.sub.3       ##STR61##       CH.sub.2 CN H O O(i)Pr NMR δ.sub.TMS.sup.CDCl.sbsp.3 : 1.25(d,      6H),3.74(s, 3H), 3.80-4.00(m, 4H), 4.68(s, 2H),5.92(s, 1H), 6.78(d,      1H),7.30(d, 1H)  76 C.sub.2 H.sub.5 C.sub.2 H.sub.5 CH.sub.2 CN H O      O(i)Pr n.sub.D.sup.17.5 1.5218 77 OCH.sub.3 CHNOH CH.sub.2 CN H O O(i)Pr      NMR δ.sub.TMS.sup.CDCl.sbsp.3 : 1.25(d, 6H),        3.82(s, 3H),      4.35(s, 2H),        8.30(s, 1H) 78 OCH.sub.3 CHNOCH.sub.3 CH.sub.2 CN H      O O(i)Pr NMR δ.sub.TMS.sup.CDCl.sbsp.3 : 1.30(d, 6H),      3.88(s, 1H), 4.76(s, 2H),       8.42(s, 1H)  79 Cl  CH.sub.2 OCH.sub.3      CH.sub.2       CN H O      ##STR62##       n.sub.D.sup.21.8 1.5190  80 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O       ##STR63##       n.sub.D.sup.21.8 1.5316  81 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O       ##STR64##       n.sub.D.sup.21.9 1.5310  82 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O       ##STR65##       n.sub.D.sup.22.4 1.5483  83 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O       ##STR66##       n.sub.D.sup.22.8 1.5426  84 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O       ##STR67##       n.sub.D.sup.21.8 1.5221  85 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O       ##STR68##       n.sub.D.sup.22.7 1.5230 86 Cl CH.sub.2 OCH.sub.3 CH.sub.2 CN H O       ##STR69##       n.sub.D.sup.23.8 1.5307  87 Cl CH.sub.2       OCH.sub.3      ##STR70##       H O O(i)Pr n.sub.D.sup.31.0 1.5306  88 Cl CH.sub.2       OCH.sub.3      ##STR71##       H O O(i)Pr n.sub.D.sup.31.0 1.5365 89 Cl CH.sub.2       OCH.sub.3      ##STR72##       H O O(i)Pr n.sub.D.sup.26.0 1.5181  90 Cl CH.sub.2       OCH.sub.3      ##STR73##       H O O(i)Pr n.sub.D.sup.26.0 1.5259  91 Cl CH.sub.2 OCH.sub.3 CH.sub.2      CH.sub.2 OH H O O(i)Pr n.sub.D.sup.23.0 1.5200 92 Cl CH.sub.2 OCH.sub.3      CH.sub.2 CHCHCH.sub.2 OCH.sub.3 H O O(i)Pr n.sub.D.sup.24.4 1.5193 93 Cl C      H.sub.2 OCH.sub.3 CH.sub.2 CCCH.sub.2       OCH.sub.3 H O O(i)Pr n.sub.D.sup.24.4 1.5297  94 Cl CH.sub.2 OCH.sub.3      CH.sub.2       CN H O      ##STR74##        95 OC.sub.2 H.sub.5 CHBrCH.sub.2 Br CH.sub.2 CN H O O(i)Pr 96 CH.sub.3 C      HNOH CH.sub.2       CN H O O(i)Pr

In the practical usage of the compounds of the formula (I) as fungicides, they may be applied as such or in a formulation form such as dusts, wettable powders, oil sprays, emulsifiable concentrates, tablets, granules, fine granules, aerosols or flowables. Such formulation form can be formulated in a conventional manner by mixing at least one of the compounds of the formula (I) with an appropriate solid or liquid carrier(s) or diluent(s) and, if necessary, an appropriate adjuvant(s) (e.g. surfactants, adherents, dispersants, stabilizers) for improving the dispersibility and other properties of the active ingredient.

Examples of the solid carriers or diluents are botanical materials (e.g. flour, tobacco stalk powder, soybean powder, walnut-shell powder, vegetable powder, saw dust, bran, bark powder, cellulose powder, vegetable extract residue), fibrous materials (e.g. paper, corrugated cardboard, old rags), synthetic plastic powders, clays (e.g. kaolin, bentonite, fuller's earth), talcs, other inorganic materials (e.g. pyrophyllite, sericite, pumice, sulfur powder, active carbon) and chemical fertilizers (e.g. ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride).

Examples of the liquid carriers or diluents are water, alcohols (e.g. methanol, ethanol), ketones (e.g. acetone, methylethylketone), ethers (e.g. diethyl ether, dioxane, cellosolve, tetrahydrofuran), aromatic hydrocarbons (e.g. benzene, toluene, xylene, methyl naphthalene), aliphatic hydrocarbons (e.g. gasoline, kerosene, lamp oil), esters, nitriles, acid amides (e.g. dimethylformamide, dimethylacetamide), halogenated hydrocarbons (e.g. dichloroethane, carbon tetrachloride), etc.

Examples of the surfactants are alkyl sulfuric esters, alkyl sulfonates, alkylaryl sulfonates, polyethylene glycol ethers, polyhydric alcohol esters, etc. Examples of the adherents and dispersants may include casein, gelatin, starch powder, carboxymethyl cellulose, gum arabic, alginic acid, lignin, bentonite, molasses, polyvinyl alcohol, pine oil and agar. As the stabilizers, there may be used PAP (isopropyl acid phosphate mixture), tricresyl phosphate (TCP), tolu oil, epoxydized oil, various surfactants, various fatty acids and their esters, etc.

The foregoing formulations generally contain at least one of the compounds of the formula (I) in a concentration of about 1 to 95% by weight, preferably of 2.0 to 80% by weight. By using the formulations, the compounds of the formula (I) are generally applied in such amounts as 2 to 100 g per 10 are.

When only the drug-resistant strains of phytopathogenic fungi are present, the compounds of the formula (I) may be used alone. However, when the drug-sensitive strains are present together with the drug-resistant strains, their alternate use with benzimidazole, thiophanate and/or cyclic imide fungicides or their combined use with benzimidazole, thiophanate and/or cyclic imide fungicides is favorable. In such alternate or combined use, each active ingredient may be employed as such or in conventional agricultural formulation forms. In case of the combined use, the weight proportion of the compound of the formula (I) and the benzimidazole, thiophanate and/or cyclic imide fungicide may be from about 1:0.1 to 1:10.0.

Typical exmaples of the benzimidazole, thiophanate and cyclic imide fungicides are shown in Table 2.

                                      TABLE 2                                      __________________________________________________________________________     Compound                                                                             Structure            Name                                                __________________________________________________________________________            ##STR75##           Methyl 1-(butyl-carbamoyl)benz- imidazol-2-yl-c                                arbamate                                            B                                                                                     ##STR76##           2-(4-Thiazolyl)benzimidazole                        C                                                                                     ##STR77##           Methyl benzimidazole-2-ylcarbamate                  D                                                                                     ##STR78##           2-2(2-Furyl)benzimidazole                           E                                                                                     ##STR79##           1,2-Bis(3-methoxycarbonyl-2- thioureido)benzene     F                                                                                     ##STR80##           1,2-Bis(3-ethoxycarbonyl-2- thioureido)benzene      G                                                                                     ##STR81##           2-(O,SDimethyl-phosphoryl- amino)-1-(3'-methoxy                                carbonyl- 2'-thioureido)benzene                     H                                                                                     ##STR82##           2-(O,ODimethylthio- phosphorylamino)-1-(3'-meth                                oxy- carbonyl-2'-thioureido)benzene                 I                                                                                     ##STR83##           N(3',5'-Dichlorophenyl)-1,2- dimethyl-cycloprop                                ane-1,2-di- carboximide                             J                                                                                     ##STR84##           3-(3',5'-Dichlorophenyl)-1-isopropyl- carbamoyl                                imidazolidin-2,4-dione                              K                                                                                     ##STR85##           3-(3',5'-Dichlorophenyl)-5-methyl- 5-vinyloxazo                                lidin-2,4-dione                                     L                                                                                     ##STR86##           Ethyl (RS)3-(3',5'-dichlorophenyl)- 5-methyl-2,                                4-dioxooxazolidine-5- carboxylate                   __________________________________________________________________________

Besides, the compounds of the formula (I) may be also used in admixture with other fungicides, herbicides, insecticides, miticides, fertilizers, etc.

When the compounds of the formula (I) are used as fungicides, they may be applied in such amounts as 2 to 100 grams per 10 ares. However, this amount may vary depending upon formulation forms, application times, application methods, application sites, diseases, crops and so on, and therefore, they are not limited to said particular amounts.

Some practical embodiments of the fungicidal composition according to the invention are illustratively shown in the following Examples wherein % and part(s) are by weight.

FORMULATION EXAMPLE 1

Two parts of Compound No. 5, 88 parts of clay and parts of talc are thoroughly pulverized and mixed together to obtain a dust formulation containing 2% of the active ingredient.

FORMULATION EXAMPLE 2

Thirty parts of Compound No. 12, 45 parts of diatomaceous earth, 20 parts of white carbon, 3 parts of sodium laurylsulfate as a wetting agent and 2 parts of calcium ligninsulfonate as a dispersing agent are mixed while being powdered to obtain a wettable powder formulation containing 30% of the active ingredient.

FORMULATION EXAMPLE 3

Fifty parts of Compound No. 13, 45 parts of diatomaceous earth, 2.5 parts of calcium alkylbenzenesulfonate as a wetting agent and 2.5 parts of calcium ligninsulfonate as a dispersing agent are mixed while being powdered to obtain a wettable powder formulation containing 50% of the active ingredient.

FORMULATION EXAMPLE 4

Ten parts of Compound No. 17, 80 parts of cyclohexanone and 10 parts of polyoxyethylene alkylaryl ether as an emulsifier are mixed together to obtain an emulsifiable concentrate formulation containing 10% of the active ingredient.

FORMULATION EXAMPLE 5

One part of Compound No. 5, 1 part of Compound No. I, 88 parts of clay and 10 parts of talc are thoroughly pulverized and mixed together to obtain a dust formulation containing 2% of the active ingredient.

FORMULATION EXAMPLE 6

Twenty parts of Compound No. 3, 10 parts cf Compound J, 45 parts of diatomaceous earth, 20 parts of white carbon, 3 parts of sodium laurylsulfate as a wetting agent and 2 parts of calcium ligninsulfonate as a dispersing agent are mixed while being powdered to obtain a wettable powder formulation containing 30% of the active ingredient.

FORMULATION EXAMPLE 7

Ten parts of Compound No. 13, 40 parts of Compound A, 45 parts of diatomaceous earth, 2.5 parts of calcium alkylbenzenesulfonate as a wetting agent and 2.5 parts of calcium ligninsulfonate as a dispersing agent are mixed while being powdered to obtain a wettable powder formulation containing 50% of the active ingredient.

Typical test data indicating the excellent fungicidal activity of the compounds of the formula (I) are shown below. The compounds used for comparison are as follows:

    ______________________________________                                         Compound             Remarks                                                   ______________________________________                                         Swep                                                                            ##STR87##           Commercially available herbicide                          Chlorpropham                                                                    ##STR88##           Commercially available herbicide                          Baraban                                                                         ##STR89##           Commercially available herbicide                          CEPC                                                                            ##STR90##           Commercially available herbicide                          Propham                                                                         ##STR91##           Commercially available herbicide                          Chlorbufam                                                                      ##STR92##           Commercially available herbicide                          Benomyl                                                                         ##STR93##           Commercially available fungicide                          Thiophanate-methyl                                                              ##STR94##           Commercially available fungicide                          Carbendazim                                                                     ##STR95##           Commercially available fungicide                          ______________________________________                                    

EXPERIMENT 1

Protective activity test on powdery mildew of cucumber (Sphaerotheca fuliginea):

A flower pot of 90 ml volume was filed with sandy soil, and seeds of cucumber (var: Sagami-hanjiro) were sowed therein. Cultivation was carried out in a greenhouse for 8 days. Onto the resulting seedlings having cotyledons, the test compound formulated in an emulsifiable concentrate or wettable powder and diluted with water was sprayed at a rate of 10 ml per pot. Then, the seedlings were inoculated with a spore suspension of the drug-resistant or drug-sensitive strain of Sphaerotheca fuliginea by spraying and further cultivated in the greenhouse. Ten days thereafter, the infectious state of the plants was observed. The degree of damage was determined in the following manner, and the results are shown in Table 3.

The leaves examined were measured for a percentage of infected area and classified into the corresponding disease indices, 0, 0.5, 1, 2, 4:

    ______________________________________                                         Disease index Percentage of infected area                                      ______________________________________                                         0             No infection                                                     0.5           Infected area of less than 5%                                    1             Infected area of less than 20%                                   2             Infected area of less than 50%                                   4             Infected area of not less than 50%                               ______________________________________                                    

The disease severity was calculated according to the following equation: ##EQU1##

The prevention value was calculated according to the following equation: ##EQU2##

                  TABLE 3                                                          ______________________________________                                                                Prevention  Prevention                                                         value when  value when                                             Concentration                                                                              inoculated  inoculated                                             of active   with drug-  with drug-                                  Compound   ingredient  resistant   sensitive                                   No.        (ppm)       strain (%)  strain (%)                                  ______________________________________                                          2         500         100         0                                            3         500         100         0                                            4         500         100         0                                            5         200         100         0                                           12         200         100         0                                           13         200         100         0                                           Swep       200         0           0                                           Chlorpropham                                                                              200         0           0                                           Barban     200         25          0                                           CEPC       200         0           0                                           Propham    200         0           0                                           Chlorbufam 200         0           0                                           Benomyl    200         0           100                                         Thiophanate-                                                                              200         0           100                                         methyl                                                                         Carbendazim                                                                               200         0           100                                         ______________________________________                                    

As understood from the results shown in Table 3, the compounds of the formula (I) of the invention shown an excellent preventive effect on the drug-resistant strain but do not show any preventive effect on the tested drug-sensitive strain. To the contrary, commercially available known fungicides such as Benomyl, Thiophanate-methyl and Carbendazim show a notable controlling effect on the drug-sensitive strain but not on the drug-resistant strain. Other tested compounds structurally similar to the compounds of the formula (I) do not show any fungicidal activity on the drug-sensitive strain and the drug-resistant strain.

Experiment 2

Preventive effect on cercospora leaf spot of sugarbeet (Cercospora beticola):

A flower pot of 90 ml volume was filled with sandy soil, and seeds of sugarbeet (var: Detroit dark red) were sowed therein. Cultivation was carried out in a greenhouse for 20 days. Onto the resulting seedlings, the test compound formulated in an emulsifiable concentrate or wettable powder and diluted with water was sprayed at a rate of 10 ml per pot. Then, the seedlings were inoculated with a spore suspension of the drug-resistant or drug-sensitive strain of Cercospora beticola by spraying. The pot was covered with a polyvinyl chloride sheet to make a condition of high humidity, and cultivation was continued in the greenhouse for 10 days. The degree of damage was determined in the same manner as in Experiment 1, and the results are shown in Table 4.

                  TABLE 4                                                          ______________________________________                                                                Prevention  Prevention                                                         value when  value when                                             Concentration                                                                              inoculated  inoculated                                             of active   with drug-  with drug-                                  Compound   ingredient  resistant   sensitive                                   No.        (ppm)       strain (%)  strain (%)                                  ______________________________________                                          2         500         100         0                                            3         500         100         0                                            4         500         100         0                                            5         200         100         0                                           12         200         100         0                                           13         200         100         0                                           15         200         100         0                                           17         200         100         0                                           18         200         100         0                                           Swep       200         0           0                                           Chlorpropham                                                                              200         0           0                                           Barban     200         34          0                                           CEPC       200         0           0                                           Propham    200         0           0                                           Chlorbufam 200         0           0                                           Benomyl    200         0           100                                         Thiophanate-                                                                              200         0           100                                         methyl                                                                         Carbendazim                                                                               200         0           100                                         ______________________________________                                    

As understood from the results shown in Table 4, the compounds of the formula (I) of the invention show an excellent preventive effect on the drug-resistant strain but do not show any preventive effect on the tested drug-sensitive strain. To the contrary, commercially available known fungicides such as Benomyl, Thiophanate-methyl and Carbendazim show a notable controlling effect on the drug-sensitive strain but not on the drug-resistant strain. Other tested compounds structurally similar to the compounds of the formula (I) do not show any fungicidal activity on the drug-sensitive strain and the drug-resistant strain.

Experiment 3

Preventive effect on scab of pear (Venturia nashicola):

A plastic pot of 90 ml volume was filled with sandy soil, and seeds of pear (var:Chojuro) were sowed therein. Cultivation was carried out in a greenhouse for 20 days. Onto the resulting seedlings, the test compound formulated in an emulsifiable concentrate or wettable powder and diluted with water was sprayed at a rate of 10 ml per pot. Then, the seedlings were inoculated with a spore suspension of the drug-resistant or drug-sensitive strain of Venturia nashicola by spraying. The resulting plants were placed at 20° C. under a condition of high humidity for 3 days and then at 20° C. under irradiation with a fluorescent lamp for 20 days. The degree of damage was determined in the same manner as in Experiment 1, and the results are shown in Table 5.

                  TABLE 5                                                          ______________________________________                                                                Prevention                                                                               Prevention                                                           value when                                                                               value when                                             Concentration inoculated                                                                               inoculated                                             of active     with drug-                                                                               with drug-                                    Compound ingredient    resistant sensitive                                     No.      (ppm)         strain (%)                                                                               strain (%)                                    ______________________________________                                          2       500           100       0                                              3       500           100       0                                              4       500           100       0                                              5       200           100       0                                             12       200           100       0                                             13       200           100       0                                             15       200           100       0                                             18       200           100       0                                             Benomyl  200            0        100                                           Thiophanate-                                                                            200            0        100                                           methyl                                                                         ______________________________________                                    

As understood from the results shown in Table 5, the compounds of the formula (I) of the invention show an excellent preventive effect on the drug-resistant strain but do not show any preventive effect on the tested drug-sensitive strain. To the contrary, commercially available known fungicides such as Benomyl and Thiophanate-methyl show a notable controlling effect on the drug-sensitive strain but not on the drug-resistant strain.

Experiment 4

Preventive effect on brown leaf-spot of peanut (Cerospora arachidicola):

Plastic pots of 90 ml volume were filled with sandy soil, and seeds of peanut (var:Chiba hanryusei) were sowed therein. Cultivation was carried out in a greenhouse for 14 days. Onto the resulting seedling, the test compound formulated in an emulsifiable concentrate or wettable powder and diluted with water was sprayed at a rate of 10 ml per pot. Then, the seedlings were inoculated with a spore suspension of the drug-resistant or drug-sensitive strain of Cercospora arachidicola by spraying. The resulting plants were covered with a polyvinyl chloride sheet to make a condition of humidity and cultivated in the greenhouse for 10 days. The degree of damage was determined in the same manner as in Experiment 1, and the results are shown in Table 6.

                  TABLE 6                                                          ______________________________________                                                                Prevention                                                                               Prevention                                                           value when                                                                               value when                                             Concentration inoculated                                                                               inoculated                                             of active     with drug-                                                                               with drug-                                    Compound ingredient    resistant sensitive                                     No.      (ppm)         strain (%)                                                                               strain (%)                                    ______________________________________                                          5       200           100       0                                             12       200           100       0                                             13       200           100       0                                             15       200           100       0                                             19       200            98       0                                             Benomyl  200            0        100                                           Thiophanate-                                                                            200            0        100                                           methyl                                                                         ______________________________________                                    

As understood from the results shown in Table 6, the compounds of the formula (I) of the invention show an excellent preventive effect on the drug-resistant strain but do not show any preventive effect on the tested drug-sensitive strain. To the contrary, commercially available known fungicides such as Benomyl and Thiophanate-methyl show a notable controlling effect on the drug-sensitive strain but not on the drug-resistant strain.

Experiment 5

Preventive effect on gray mold of cucumber (Botrytis cinerea):

Plastic pots of 90 ml volume was filled with sandy soil, and seeds of cucumber (var:Sagami-hanjiro) was sowed therein. Cultivation was carried out in a greenhouse for 8 days to obtain cucumber seedlings expanding cotyledons. Onto the resulting seedlings, the test compound formulated in an emulsifiable concentrate or wettable powder and diluted with water was sprayed at a rate of 10 ml per pot. After air-drying, the seedlings were inoculated with mycelial disks (5 mm in diameter) of the drug-resistant or drug-sensitive strain of Botrytis cinerea by putting them on the leaf surfaces. After the plants were infected by incubating under high humidity at 20° C. for 3 days, the rates of disease severity were observed. The degree of damage was determined in the same manner as in Experiment 1, and the results are shown in Table 7.

                  TABLE 7                                                          ______________________________________                                                                Prevention                                                                               Prevention                                                           value when                                                                               value when                                             Concentration inoculated                                                                               inoculated                                             of active     with drug-                                                                               with drug-                                    Compound ingredient    resistant sensitive                                     No.      (ppm)         strain (%)                                                                               strain (%)                                    ______________________________________                                          1       200           100       0                                              2       200           100       0                                              3       200           100       0                                              4       200           100       0                                              5       200           100       0                                              6       500           100       0                                              7       500           100       0                                              8       500           100       0                                              9       500           100       0                                             10       500           100       0                                             11       500           100       0                                             12       200           100       0                                             13       200           100       0                                             14       500           100       0                                             15       200           100       0                                             16       200           100       0                                             17       200           100       0                                             18       200           100       0                                             19       200           100       0                                             20       200           100       0                                             21       200           100       0                                             22       200           100       0                                             23       200           100       0                                             24       200           100       0                                             25       200           100       0                                             26       200           100       0                                             27       200           100       0                                             34       200           100       0                                             35       200           100       0                                             36       200           100       0                                             39       200           100       0                                             41       200           100       0                                             42       200           100       0                                             43       200           100       0                                             44       200           100       0                                             45       200           100       0                                             46       200           100       0                                             50       200           100       0                                             51       200           100       0                                             52       200           100       0                                             53       200           100       0                                             55       200           100       0                                             56       200           100       0                                             61       200           100       0                                             62       200           100       0                                             63       200           100       0                                             64       200           100       0                                             65       200           100       0                                             66       200           100       0                                             70       200           100       0                                             71       200           100       0                                             75       200           100       0                                             76       200           100       0                                             77       200           100       0                                             78       200           100       0                                             79       200           100       0                                             80       200           100       0                                             81       200           100       0                                             82       200           100       0                                             83       200           100       0                                             84       200           100       0                                             85       200           100       0                                             86       200           100       0                                             87       200           100       0                                             88       200           100       0                                             Benomyl  200            0        100                                           Thiophanate-                                                                            200            0        100                                           methyl                                                                         ______________________________________                                    

As understood from the results shown in Table 7, the compounds of the formula (I) of the invention show an excellent preventive effect on the drug-resistant strain but do not show any preventive effect on the tested drug-sensitive strain. To the contrary, commercailly available known fungicides such as Benomyl and Thiophanate-methyl show a notable controlling effect on the drug-sensitive strain but not on the drug-resistant strain.

Experiment 6

Preventive effect on gummy stem blight of cucumber (Mycosphaerella melonis):

Plastic pots of 90 ml volume were filled with sandy soil, and seeds of cucumber (var:Sagami-hanjiro) were sowed therein. Cultivation was carried out in a greenhouse for 8 days to obtain cucumber seedlings expanding cotyledons. Onto the resulting seedlings, the test compound formulated in an emulsifiable concentrate or wettable powder and diluted with water was sprayed at a rate of 10 ml per pot. After air-drying, the seedlings were inoculated with mycelial disks (5 mm in diameter) of the drug-resistant or drug-sensitive strain of Mycosphaerella melonis by putting them on the leaf surfaces. After the plants were infected by incubating under high humidity at 25° C. for 4 days, the rates of disease severity were observed. The degree of damage was determined in the same manner as in Experiment 1, and the results are shown in Table 8.

                  TABLE 8                                                          ______________________________________                                                                Prevention                                                                               Prevention                                                           value when                                                                               value when                                             Concentration inoculated                                                                               inoculated                                             of active     with drug-                                                                               with drug-                                    Compound ingredient    resistant sensitive                                     No.      (ppm)         strain (%)                                                                               strain (%)                                    ______________________________________                                          5       200           100       0                                             12       200           100       0                                             13       200           100       0                                             17       200           100       0                                             Benomyl  200            0        100                                           Thiophanate-                                                                            200            0        100                                           methyl                                                                         ______________________________________                                    

As understood from the results shown in Table 8, the compounds of the formula (I) of the invention show an excellent preventive effect on the drug-resistant strain but do not show any preventive effect on the tested drug-sensitive strain. To the contrary, commercially available known fungicides such as Benomyl and Thiophanate-methyl show a notable controlling effect on the drug-sensitive strain but not on the drug-resistant strain.

Experiment 7

Preventive effect on green mold of orange (Penicillium italicum):

Fruits of orange (var:Unshu) were washed with water and dried in the air. The fruits were immersed in a solution of the test compound prepared by diluting an emulsifiable concentrate comprising the test compound with water for 1 minute. After drying in the air, the fruits were inoculated with a spore suspension of the drug-resistant or drug-sensitive strain of Penicillium italicum by spraying and placed in a room of high humidity for 14 days. The degree of damage was determined in the following manner:

The fruits examined were measured for a percentage of infected area and classified into the corresponding indices, 0, 1, 2, 3, 4, 5:

    ______________________________________                                         Disease index Percentage of infected area                                      ______________________________________                                         0             No infection                                                     1             Infected area of less than 20%                                   2             Infected area of less than 40%                                   3             Infected area of less than 60%                                   4             Infected area of less than 80%                                   5             Infected area of not less than 80%                               ______________________________________                                    

Calculation of the degree of damage and the prevention value was made as in Experiment 1.

The results are shown in Table 9.

                  TABLE 9                                                          ______________________________________                                                                Prevention                                                                               Prevention                                                           value when                                                                               value when                                             Concentration inoculated                                                                               inoculated                                             of active     with drug-                                                                               with drug-                                    Compound ingredient    resistant sensitive                                     No.      (ppm)         strain (%)                                                                               strain (%)                                    ______________________________________                                          5       200           100       0                                             12       200           100       0                                             13       200           100       0                                             15       200           100       0                                             18       200           100       0                                             Benomyl  200            0        100                                           Thiophanate-                                                                            200            0        100                                           methyl                                                                         ______________________________________                                    

As understood from the results shown in Table 9, the compounds of the formula (I) of the invention show an excellent preventive effect on the drug-resistant strain but do not show any preventive effect on the tested drug-sensitive strain. To the contrary, commercially available known fungicides such as Benomyl and Thiophanate-methyl show a notable controlling effect on the drug-sensitive strain but not on the drug-resistant strain.

Experiment 8

Phytotoxicity on crop plants:

Plastic pots of 150 ml volume were filled with sandy soil, and seeds of wheat (var:Norin No, 61), apple (var:Kogyoku) and peanut (var:Chiba hanryusei) were sowed therein. Cultivation was carried out in a greenhouse. Onto the resulting seedlings, the test complund formulated in an emulsifiable concentrate of wettable powder and diluted with water was sprayed. After cultivation in the greenhouse for an additonal 10 days, the phytotosicity was examined on the following criteria:

    ______________________________________                                         Extent     Observation                                                         ______________________________________                                         -          No abnormality                                                      +          Abnormality due to phytotoxicity observed                                      in a part of crop plants                                            ++         Abnormality due to phytotoxicity observed                                      in entire crop plants                                               +++        Crop plants withered due to phytotoxicity                           ______________________________________                                    

The results are shown in Table 10

                  TABLE 10                                                         ______________________________________                                                   Concentration                                                                  of active                                                            Compound  ingredient  Phytotoxicity                                            No.       (ppm)       Wheat     Apple Peanut                                   ______________________________________                                          5        1000        -         -     -                                        12        1000        -         -     -                                        13        1000        -         -     -                                        Barban    1000        -         ++    ++                                       CEPC      1000        -         ++    ++                                       Swep      1000        ++        ++    +                                        ______________________________________                                    

As understood from the results shown in Table 10, the compounds of the formula (I) of the invention produce no material phytotoxicity, while commercially available herbicides having a chemical structure similar thereto produce considerable phytotoxicity.

Experiment 9

Preventive effect on powdery mildew of cucumber (Sphaerotheca fuliginea):

A plastic pot of 90 ml volume was filled with sandy soil, and seeds of cucumber (var:Sagami-hanjiro) were sowed therein. Cultivation was carried out in a greenhouse for 8 days. Onto the resulting seedlings having cotyledons, the test compound(s) formulated in an emulsifiable concentrate or wettable powder and diluted with water were sprayed at a rate of 10 ml per pot. Then, the seedlings were inoculated with a mixed spore suspension of the drug-resistant and drug-sensitive strain of Sphaerotheca fuliginea by spraying and further cultivated in the greenhouse. Ten days thereafter, the infectious state of the plants was observed. The degree of damage was determined in the same manner as in Experiment 1, and the results are shown in Table 11.

                  TABLE 11                                                         ______________________________________                                                       Concentration of                                                                            Prevention                                                        active ingredient                                                                           value                                               Compound No.  (ppm)        (%)                                                 ______________________________________                                          2            100          40                                                   2             20          0                                                    3            100          42                                                   3             20          0                                                    4            100          34                                                   4             20          0                                                    5            100          45                                                   5             20          0                                                   12            100          38                                                  12             20          0                                                   13            100          36                                                  13             20          0                                                   17            100          40                                                  17             20          0                                                   18            100          36                                                  18             20          0                                                   A             100          45                                                  A              20          12                                                  B             500          42                                                  B             100          10                                                  C             100          42                                                  C              20          8                                                   D             500          36                                                  D             100          0                                                   E             100          44                                                  E              20          10                                                  F             100          43                                                  F              20          8                                                   G             100          42                                                  G              20          8                                                   H             100          40                                                  H              20          5                                                   2 + A         20 + 20      100                                                 2 + B         20 + 20      100                                                 2 + E         20 + 20      100                                                 2 + G         20 + 20      100                                                 3 + C         20 + 20      100                                                 3 + D         20 + 20      100                                                 3 + F         20 + 20      100                                                 3 + H         20 + 20      100                                                 4 + A         20 + 20      100                                                 4 + D         20 + 20      100                                                 4 + E         20 + 20      100                                                 4 + G         20 + 20      100                                                 5 + A         20 + 20      100                                                 5 + B         20 + 20      100                                                 5 + E         20 + 20      100                                                 5 + G         20 + 20      100                                                 12 + C        20 + 20      100                                                 12 + D        20 + 20      100                                                 12 + F        20 + 20      100                                                 12 + H        20 + 20      100                                                 13 + A        20 + 20      100                                                 13 + D        20 + 20      100                                                 13 + E        20 + 20      100                                                 13 + G        20 + 20      100                                                 17 + A        20 + 20      100                                                 17 +  B       20 + 20      100                                                 17 + E        20 + 20      100                                                 17 + G        20 + 20      100                                                 18 + C        20 + 20      100                                                 18 + D        20 + 20      100                                                 18 + F        20 + 20      100                                                 18 + H        20 + 20      100                                                 ______________________________________                                    

As understood from the results shown in Table 11, the combinated use of the compounds of the formula (I) of the invention with benzimidazole, thiophanate and/or cyclic imide fungicides show much more excellent preventive effect than their sole use.

Experiment 10

Preventive effect on gray mold of tomato (Botrytis cinerea):

A plastic pot of 90 ml volume was filled with sandy soil, and seeds of tomato (var:Fukuju No. 2) were sowed therein. Cultivation was carried out in a greenhouse for 4 weeks. Onto the resulting seedlings at the 4-leaf stage, the test compound(s) formulated in an emulsifiable concentrate or wettable powder and diluted with water were sprayed at a rate of 10 ml per pot. Then, the seedlings were inoculated with a mixed spore suspension of the drug-resistant and drug-sensitive strain of Botrytis cinerea by spraying and placed at 20° C. in a room of high humidity for 5 days. The degree of damage was determined in the same manner as in Experiment 1, and the results are shown in Table 12.

                  TABLE 12                                                         ______________________________________                                                       Concentration of                                                                            Prevention                                                        active ingredient                                                                           value                                               Compound No.  (ppm)        (%)                                                 ______________________________________                                          2            100          32                                                   2             20          0                                                    3            100          44                                                   3             20          0                                                    4            100          44                                                   4             20          0                                                    5            100          38                                                   5             20          0                                                   12            100          40                                                  12             20          0                                                   13            100          42                                                  13             20          0                                                   15            100          43                                                  15             20          0                                                   I             100          48                                                  I              20          22                                                  J             500          46                                                  J             100          18                                                  K             100          42                                                  K              20          15                                                  L             500          42                                                  L             100          12                                                   2 + I        20 + 50      100                                                  2 + J        20 + 50      100                                                  3 + I        20 + 50      100                                                  3 + K        20 + 50      100                                                  4 + I        20 + 50      100                                                  4 + J        20 + 50      100                                                  4 + K        20 + 50      100                                                  4 + L        20 +  50     100                                                  5 + I        20 + 50      100                                                  5 + J        20 + 50      100                                                 12 + I        20 + 50      100                                                 12 + K        20 + 50      100                                                 13 + I        20 + 50      100                                                 13 + J        20 + 50      100                                                 13 + K        20 + 50      100                                                 13 + L        20 + 50      100                                                 15 + I        20 + 50      100                                                 15 + J        20 + 50      100                                                 ______________________________________                                    

As understood from the results shown in Table 12, the combined use of the compounds of the formula (I) of the invention with benzimidazole, thiophanate and/or cyclic imide fungicides show much more excellent preventive effect than their sole use. 

What is claimed is:
 1. A compound of the formula: ##STR96## wherein X is a halogen atom; R¹ is a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a halo (lower) alkyl group or a lower alkoxy (lower) alkyl group; R² and R³ are both a lower alkyl group.
 2. The composition of claim 1, wherein the active ingredient is a compound represented by the formula: ##STR97##
 3. A fungicidal composition which comprises as an essential active ingredient a fungicidally effective amount of a compound according to claim 1, and an inert carrier or diluent.
 4. A method for controlling plant pathogenic fungi which comprises applying a fungicially effective amount of at least one compound according to claim 1 to plant pathogenic fungi.
 5. The method according to claim 4, wherein the plant pathogenic fungi is the drug-resistant strain. 